N-terminal protein amino acid modification

Definition

Target type: biologicalprocess

The alteration of the N-terminal amino acid residue in a protein. [GOC:mah]

N-terminal protein amino acid modification is a fundamental process in cellular biology that plays a crucial role in regulating protein function, stability, and localization. It involves the enzymatic modification of the N-terminal amino acid residue of a newly synthesized protein, often occurring co-translationally. This modification can dramatically alter the protein's properties and determine its fate within the cell.

The N-terminus of a protein is typically characterized by a methionine residue, encoded by the start codon AUG. However, this methionine is often removed or modified through a series of enzymatic steps. These modifications can involve:

1. **Methionine Removal:** The N-terminal methionine can be cleaved by methionine aminopeptidase (MetAP), a ubiquitous enzyme present in all organisms. MetAP recognizes the N-terminal methionine and its adjacent residue. The presence of bulky or negatively charged residues at the second position (P2) generally favors cleavage. This removal is critical for the proper folding, stability, and activity of many proteins.

2. **Acetylation:** N-terminal acetylation is a widespread modification where an acetyl group (CH3CO) is added to the α-amino group of the N-terminal residue. This modification is catalyzed by N-terminal acetyltransferases (NATs), which are diverse and can exhibit substrate specificity. Acetylation can enhance protein stability by protecting the N-terminus from proteolytic degradation, promote proper folding, and facilitate protein-protein interactions.

3. **Myristoylation:** This modification involves the attachment of myristate, a 14-carbon saturated fatty acid, to the N-terminal glycine residue. This modification is catalyzed by N-myristoyltransferases (NMTs) and is often found in proteins involved in membrane association, signal transduction, and protein-protein interactions.

4. **Other Modifications:** Additional modifications at the N-terminus include:
* **Glycosylation:** The addition of sugar moieties to the N-terminus, often found in secreted proteins.
* **Phosphorylation:** The addition of a phosphate group, which can regulate protein activity and localization.
* **Ubiquitylation:** The attachment of ubiquitin, a small protein that can target proteins for degradation.

The specific N-terminal modifications that occur on a given protein are determined by its amino acid sequence, cellular localization, and function. These modifications are crucial for proper protein function and play significant roles in various cellular processes, including:

* **Protein folding and stability:** N-terminal modifications can influence protein folding and stability by affecting interactions with chaperones and other proteins.
* **Protein trafficking and localization:** Modifications can direct proteins to specific cellular compartments or membranes.
* **Protein-protein interactions:** N-terminal modifications can create or alter binding sites for other proteins.
* **Protein activity:** N-terminal modifications can activate or inhibit protein function.

In summary, N-terminal protein amino acid modification is a complex and diverse process that plays a vital role in regulating protein function and fate within the cell. Understanding these modifications is critical for comprehending the intricate mechanisms of cellular processes and for developing therapeutic strategies targeting protein function.'
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Proteins (3)

Compounds (20)